Neural correlates of the LSD experience revealed by multimodal neuroimaging
Open accessAbstract
Significance: Lysergic acid diethylamide (LSD), the prototypical “psychedelic,” may be unique among psychoactive substances. In the decades that followed its discovery, the magnitude of its effect on science, the arts, and society was unprecedented. LSD produces profound, sometimes life-changing experiences in microgram doses, making it a particularly powerful scientific tool. Here we sought to examine its effects on brain activity, using cutting-edge and complementary neuroimaging techniques in the first modern neuroimaging study of LSD. Results revealed marked changes in brain blood flow, electrical activity, and network communication patterns that correlated strongly with the drug’s hallucinatory and other consciousness-altering properties. These results have implications for the neurobiology of consciousness and for potential applications of LSD in psychological research.
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Disruption of the salience network is believed to be associated with the experience of ego dissolution.
“Such disruption is believed to be associated with the experience of ego dissolution [71].”
From Mindfulness meditation and psychedelics: potential synergies and commonalities (2023) · cites this paper as [71]
The Results (p. 3) identify reduced segregation between the default mode and salience networks under LSD, but report that reduced network segregation did not correlate with ego-dissolution. They instead find a significant correlation with default mode network disintegration; correlations with the integrity of the other 11 networks were not significant. (LLM, conf=0.86)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredReduced mPFC-PCC connectivity as well as DMN deactivation and disintegration have been demonstrated post-acutely after the administration of psilocybin, LSD and ayahuasca.
“In the field of psychedelic neuroscience, reduced mPFC-PCC connectivity as well as DMN deactivation and disintegration have been demonstrated post-acutely after the administration of psilocybin, LSD and ayahuasca (45, 46, 57), while long-term ayahuasca users demonstrated thinning of the PCC (117).”
From Examining the Potential Synergistic Effects Between Mindfulness Training and Psychedelic-Assisted Therapy (2021) · cites this paper as [46]
The Discussion (p. 4) reports decreased DMN integrity and network disintegration under LSD. But the study explicitly investigated acute effects: scans occurred during peak subjective effects (p. 2), not post-acutely. The cited passages also do not establish reduced mPFC–PCC connectivity or DMN deactivation specifically. (LLM, conf=0.88)
Experimental — accuracy not yet measuredASL measurements indicated that LSD increased CBF in visual cortex of human volunteers.
“In contrast, arterial spin labeling (ASL) measurements of cerebral perfusion indicated that LSD (1) increased CBF in visual cortex of human volunteers [139].”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [139]
The increased CBF and the extent of functional connectivity of the visual cortex correlated with the intensity of visual hallucinations.
“The increased CBF and the extent of the functional connectivity of the visual cortex correlated with the intensity of visual hallucinations; we suppose that anesthesia may have interfered in the effects of LSD (1) on CBF in the pig PET study.”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [139]
Certain psychedelic studies have correlated transient connectivity changes within the DMN with subjective measures of drug-induced ego-dissolution.
“Certain psychedelic studies have further correlated these transient connectivity changes within the DMN with subjective measures of drug-induced ego-dissolution (46, 115).”
From Examining the Potential Synergistic Effects Between Mindfulness Training and Psychedelic-Assisted Therapy (2021) · cites this paper as [46]
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Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials
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Microdosing with psilocybin mushrooms: a double-blind placebo-controlled study
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Self-citationHarmonic brain modes: a unifying framework for linking space and time in brain dynamics
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Updating the dynamic framework of thought: Creativity and psychedelics
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Self-citationd-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology
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Distributed harmonic patterns of structure-function dependence orchestrate human consciousness
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- Authors
- Carhart-Harris, R. L., Muthukumaraswamy, S., Roseman, L., Kaelen, M., Droog, W., Murphy, K., Tagliazucchi, E., Schenberg, E. E., Nest, T., Orban, C., Leech, R., Williams, L. T., Williams, T. M., Bolstridge, M., Sessa, B., McGonigle, J., Sereno, M. I., Nichols, D., Hellyer, P. J., Hobden, P., Evans, J., Singh, K. D., Wise, R. G., Curran, H. V., Feilding, A., & Nutt, D. J.
- Affiliations
- Imperial College London (GB)
- University of Auckland (NZ)
- Cardiff University (GB)
- Goethe University Frankfurt (DE)
- McGill University (CA)
- Centre for Neuropsychopharmacology, Department of Medicine, Imperial College London, W12 0NN, London, United Kingdom;
- Department of Psychiatry, University of Bristol, BS8 2BN, Bristol, United Kingdom;
- University College London (GB)
- University of North Carolina at Chapel Hill (US)
- Beckley Foundation (GB)
- ORCID
- Carhart-Harris, Robin L.
- Muthukumaraswamy, Suresh
- Roseman, Leor
- Kaelen, Mendel
- Droog, Wouter
- Murphy, Kevin
- Tagliazucchi, Enzo
- Schenberg, Eduardo E.
- Leech, Robert
- Sessa, Ben
- McGonigle, John
- Sereno, Martin I.
- Nichols, David
- Hellyer, Peter J.
- Evans, John
- Singh, Krish D.
- Wise, Richard G.
- Curran, H. Valerie
- Feilding, Amanda
- Nutt, David J.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-04-11
- Volume
- 113
- Issue
- 17
- Pages
- 4853-4858
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4855588
- OpenAlex
- W2336389811
- Cited by
- 859
- References
- 47
- Citations by year
- 2026: 79 · 2025: 85 · 2024: 110 · 2023: 112 · 2022: 83 · 2021: 85 · 2020: 67 · 2019: 70 · 2018: 74 · 2017: 64 · 2016: 29
- FWCI
- 105.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- BIROn (Birkbeck, University of London) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (WT090199, 200804/Z/16/Z)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
- Social Sciences › Psychology › Social Psychology › Paranormal Experiences and Beliefs
- Keywords
- lysergic acid diethylamide, LSD, psychedelics, visual hallucinations, ego dissolution, visual cortex, primary visual cortex, cerebral blood flow, alpha power, functional connectivity, parahippocampal cortex, retrosplenial cortex, consciousness, resting-state brain activity
- MeSH terms
- Brain, Brain Mapping, Cerebrovascular Circulation, Consciousness, Hallucinations, Hallucinogens, Humans, Lysergic Acid Diethylamide, Magnetic Resonance Imaging, Nerve Net, Synaptic Transmission, Oxygen, Spin Labels, Magnetoencephalography, Receptor, Serotonin, 5-HT2A, Serotonin 5-HT2 Receptor Agonists, Connectome, Multimodal Imaging
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